We are using fetal organ cultures, prepared according to Grobstein's method of transfilter metanephric induction, to study the embryonic development of the kidney and its alteration under defined and controlled conditions. The method relies on the interaction between undifferentiated metanephric blastema and suitable embryonic inducer for the differentiation of metanephric derivatives. Cellular organization and growth lead to the formation of glomeruli and tubules that have been shown to be ultrastructurally well differentiated despite the lack of vascularization and ultrafiltration. We propose to use this system for studying the effects on nephronic growth, differentiation and function of selected substrates and environmental agents. We are now, for example, studying the effect on glomerular growth and basement membrane production of glucose and other energy substrates. We hope to develop this system into a method for identifying and evaluating toxic metabolites and drugs and potential cystogenic agents. Finally, we hope to use the system for developmental studies of tubular transport.